DESCRIPTION (Applicant's abstract): The parietal cortex is a visual region that represents spatial relationships. This representation has been shown dependent on attentional state in both human and non-human primates. In the latter species, electrophysiological measurements have repeatedly shown that "attention" can alter the response of single cells in the inferior parietal lobule. Few studies have examined what physiological mechanisms underlie the modulation of the visual response. The lacuna in understanding is not limited to the parietal cortex as similar issues exist for other cortices. The current proposal will be the first to use precise neuropharmacological methods to address the issue of attentional modulation of visual responses in the cortex of behaving monkeys. The approach will be three-fold. Behavioral, electrophysiological and neuropharmacological methods will be combined in order to examine how the locus coeruleus diffuse projections may alter cortical responses. The primary hypothesis is that norepinephrine release underlies attentional modulation of neural activity in parietal cortex. Specifically norepinephrine release varies with locus coeruleus activity altering signal-to-noise processing capabilities of individual pyramidal neurons and the functional circuitry of interneurons. To test this hypothesis, monkeys will be trained to perform a behavioral task in which the attentional dimensions of difficulty and focus may be systematically manipulated. The strength and the spatial distribution of the neural representation will be quantitatively evaluated as a function of attentional state using single unit recording methods. Microdialysis will then be used to measure extracellular norepinephrine levels. Pharmacological manipulations will be performed to confirm that norepinephrine is being released at this site. Then, norepinephrine release at different attentional states will be measured. Correlations will be drawn between the electrophysiological and pharmacological measures. Strategies for restoring attentional deficits may be derived from this work.